Our major direction has been the study of the effects of C-reactive protein (CRP) upon platelet function where we have found this acute phase reactant to inhibit platelet aggregation and release reactions by a mechanism which appears to be directed at the biosynthesis and/or utilization of prostaglandin-metabolism-derived products of arachidonate; in conjunction with these studies we have begun to investigate the possible modulatory functions of other acute phase reactants upon the platelet that are either structurally similar to CRP or whose kinetics of production are like that of CRP. We have also begun studies to investigate the manner in which complement, particularly subcomponent Clq (or a Clq-like molecule), through an association with the putative platelet receptor for collagen, might enlarge the scope of molecules reactive with the platelet; to chemically define and describe the mechanism by which basophil and mast cell-derived platelet activating factor (PAF) obtained from various species activates the platelet; and have initiated studies to ascertain the possible regulatory role of the platelet lipoxygenase pathway (in association with the cyclo-oxygenase pathway) with respect to the control of levels of the cyclic nucleotides and subsequent affects upon platelet activation. Thus, our major objectives have become to define and characterize the roles of CRP and other acute phase reactants, complement (and polyanions), PAF and metabolic products formed from arachidonate in the modulation of platelet function and have proposed herein methods to achieve these goals. It is hoped that a study of this nature will contribute to a better understanding of the events which lead to both an inhibited and activated platelet state, how a number of separate biological systems integrate in this purpose and perhaps gain sufficient insight into these mechanisms to allow for their favorable external manipulation.